DESCRIPTION: (provided by the applicant) Nicotine plays an important role in maintenance of tobacco dependence. Nicotine self-administration has been studied in both nonhuman primates and rodents (i.e., Goldberg et al., 1981; Corrigall and Coen, 1989; Picciotto et al., 1998). To date, Nicotine self-administration studies in rodents have mainly used the rat as the species of choice. However, with the development of a complete genetic library in mice, the murine model is becoming an increasingly valuable tool for relating the genetic contributions to drug dependence. Thus, mouse self-administration model has become an imperative tool to examine the genetic influences in drug addiction research. However, there has been only a few studies examining nicotine administration in the mouse. Initially, nicotine self-administration was established in mice that were partially immobilized since the intravenous portal was accessed through the tail, however, later studies used the jugular vein as the intravenous portal. Studies have also examined nicotine self-administration in mice that have had previous experience with other drugs of abuse (i.e., cocaine). Additionally, nicotine self-administration has been examined in drug-naive animals using an extended 12-hour session. Thus, even though nicotine self-administration can be trained in mice, a mouse model using drug-naive mice and a more limited access schedule is needed (similar to that used to examine the rewarding effects of opiates and psychomotor stimulants). The following proposal will further develop nicotine self-administration in drug-naive mice that are not restricted in their movement and given a limited access testing period. Prior to examining nicotine self-administration in mice, the self-administration mouse model will be established in the PI's laboratory using cocaine as the experimental drug. Cocaine self-administration in mice has been well established, unlike nicotine, and will therefore provide a solid foundation for further work with nicotine. Following the establishment of nicotine self-administration, future experiments will examine the potential effects of a social stressor on nicotine self-administration as well as the role of gene/environment interactions using transgenic mice.